Helicobacter Pylori Virulence Factor Cytotoxin-Associated Gene A (CagA) Induces Vascular Calcification in Coronary Artery Smooth Muscle Cells

Int J Mol Sci. 2023 Mar 11;24(6):5392. doi: 10.3390/ijms24065392.

Abstract

Helicobacter pylori (H. pylori) has been associated with cardiovascular diseases. The pro-inflammatory H. pylori virulence factor cytotoxin-associated gene A (CagA) has been detected in serum exosomes of H. pylori-infected subjects and may exert systemic effects throughout the cardiovascular system. The role of H. pylori and CagA in vascular calcification was hitherto unknown. The aim of this study was to determine the vascular effects of CagA through human coronary artery smooth muscle cell (CASMC) osteogenic and pro-inflammatory effector gene expression as well as interleukin 1β secretion and cellular calcification. CagA upregulated bone morphogenic protein 2 (BMP-2) associated with an osteogenic CASMC phenotype switch and induced increased cellular calcification. Furthermore, a pro-inflammatory response was observed. These results support that H. pylori may contribute to vascular calcification through CagA rendering CASMCs osteogenic and inducing calcification.

Keywords: Helicobacter pylori; cardiovascular disease; coronary artery smooth muscle cells; cytotoxin-associated gene A; vascular calcification.

MeSH terms

  • Antigens, Bacterial / genetics
  • Antigens, Bacterial / metabolism
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Coronary Vessels / metabolism
  • Cytotoxins / metabolism
  • Helicobacter Infections* / complications
  • Helicobacter pylori*
  • Humans
  • Vascular Calcification* / complications
  • Vascular Calcification* / genetics
  • Virulence Factors / genetics
  • Virulence Factors / metabolism

Substances

  • Antigens, Bacterial
  • Bacterial Proteins
  • Cytotoxins
  • Virulence Factors

Grants and funding

This research was funded by Ruth and Richard Julin Foundation and Karolinska Institutet’s Research Foundation Grant, grant number 2022-02306. The authors were supported by the Swedish Research Council (Grant no. 2019-01486 and 2019-00414), the Swedish Heart and Lung Foundation (Grant no. 20210560 and 20210273), ALF Region Stockholm (Grant no RS 2019-1054 and 2021-0933), and Stiftelsen Professor Nanna Svartz fond. The sources of funding had no access to the study data and no role in the design, implementation, or reporting.